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Induction of cellular immunity in chimpanzees to human tumor associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus-immortalized autologous B cells

Item Type:Article
Title:Induction of cellular immunity in chimpanzees to human tumor associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus-immortalized autologous B cells
Creators Name:Pecher, G. and Finn, O.J.
Abstract:Aberrant glycosylation of the mucin molecule (encoded by the gene MUC-1) on human epithelial cell tumors leads to the exposure of tumor-associated epitopes recognized by patients' antibodies and cytotoxic T cells. Consequently, these epitopes could be considered targets for immunotherapy. We designed a cellular vaccine, employing, instead of tumor cells, autologous Epstein-Barr virus (EBV)-immortalized B cells as carriers of tumor-associated mucin, to take advantage of their costimulatory molecules for T-cell activation. The vaccine was tested in chimpanzees because of the identity of the human and chimpanzee MUC-1 tandem repeat sequence. EBV-immortalized B cells derived from two chimpanzees were transfected with MUC-1 cDNA, treated with glycosylation inhibitor phenyl-N-acetyl-alpha-D-galactosaminide to expose tumor-associated epitopes, irradiated, and injected subcutaneously four times at 3-week intervals. One vaccine preparation also contained cells transduced with the interleukin 2 (IL-2) cDNA and producing low levels of IL-2. Already after the first injection we found in the peripheral blood measurable frequency of cytotoxic T-cell precursors specific for underglycosylated mucin. The highest frequency observed was after the last boost, in the lymph node draining the vaccination site. Delayed-type hypersensitivity reaction to the injected immunogens was also induced, whereas no appearance of mucin-specific antibodies was seen. Long-term observation of the animals yielded no signs of adverse effects of this immunization. Autologous antigen-presenting cells, like EBV-immortalized B cells, expressing tumor-associated antigens are potentially useful immunogens for induction of cellular anti-tumor responses in vivo.
Keywords:B-Lymphocytes, Cellular Immunity, Complementary DNA, Cytotoxic T-Lymphocytes, Delayed Hypersensitivity, Glycosylation, Human Herpesvirus 4, Interleukin-2, Lymphocyte Activation, Mucin-1, Neoplasm Antibodies, Neoplasm Antigens, Post-Translational Protein Processing, Recombinant Proteins, Transformed Cell Line, Vaccination, Animals, Pan Troglodytes
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:93
Number:4
Page Range:1699-1704
Date:20 February 1996
Official Publication:http://www.pnas.org/content/93/4/1699.abstract
PubMed:View item in PubMed

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